We propose to develop and implement a computer model of drug distribution in the posterior eye, with application to transscleral and intravitreal delivery systems. This work, which will build on that of ourselves and others, will provide a quantitative, predictive tool to design drug delivery strategies. Because of the importance of age-related macular degeneration and the great challenges in delivering drug to the macula, the emphasis of this work will be on predicting transport to the macula from various delivery methods. Specific issues to address will be Prediction of biodistribution from various sources. Intravitreal injection is the major delivery route to the macula, but it is unattractive for various reasons. Transscleral delivery is appealing but unproven. New ideas are also emerging. Our software will be able to pre- screen delivery methods and identify the most attractive. Translation from animal models to humans. Drug transport in animal models may be markedly different from that in the human because of interspecies differences in eye geometry and physiology. We will develop separate models for human, rabbit, and pig, and we will thus enable prediction of delivery in humans based on experiments in animals. Vitreous Liquefaction. Drug delivery experiments are routinely performed in young animals, but most AMD sufferers are quite old and thus have experienced considerable vitreous liquefaction. The liquefied vitreous is likely to have very different transport properties from the intact vitreous, and we will explore how such differences could affect biodistribution. The proposed project relates directly to human health because of its potential to improve therapy for posterior eye diseases, especially macular degeneration, the leading cause of blindness in the elderly. The project will use computer models to improve strategies for delivering drugs to the back of the eye. Diseases such as age-related macular degeneration (the leading cause of blindness in the elderly) could be treated much more effectively if we knew how to get new drugs to the affected area. The proposed project will help use existing data and bioengineering principles to identify and guide better delivery methods. [unreadable] [unreadable] [unreadable]